Correction: The Cyprus Institute of Neurology and Genetics, an emerging paradigm of a gender egalitarian organisation.

[This corrects the article DOI: 10.1371/journal.pone.

Computational investigation of the functional landscape of the protective role that extra virgin olive oil consumption may have on chronic lymphocytic leukemia.

Background: The health benefits of the Mediterranean diet are partially attributed to the polyphenols present in extra virgin olive oil (EVOO), which have been shown to have anti-cancer properties. However, the possible effect that EVOO could have on Chronic Lymphocytic Leukemia (CLL) has not been fully explored.

Methods:  This study investigates the anti-CLL activity of EVOO through a computational multi-level data analysis procedure, focusing on the identification of shared biological functions between them.

Combining clinical and molecular data for personalized treatment in acute myeloid leukemia: A machine learning approach.

Background And Objective: The standard of care in Acute Myeloid Leukemia patients has remained essentially unchanged for nearly 40 years. Due to the complicated mutational patterns within and between individual patients and a lack of targeted agents for most mutational events, implementing individualized treatment for AML has proven difficult. We reanalysed the BeatAML dataset employing Machine Learning algorithms.

Plant Biostimulants Enhance Tomato Resilience to Salinity Stress: Insights from Two Greek Landraces.

Salinity, one of the major abiotic stresses in plants, significantly hampers germination, photosynthesis, biomass production, nutrient balance, and yield of staple crops. To mitigate the impact of such stress without compromising yield and quality, sustainable agronomic practices are required. Among these practices, seaweed extracts (SWEs) and microbial biostimulants (PGRBs) have emerged as important categories of plant biostimulants (PBs).

Democracy: A Method to Capitalise on Prior Drug Discovery Efforts to Highlight Candidate Drugs for Repurposing.

In the area of drug research, several computational drug repurposing studies have highlighted candidate repurposed drugs, as well as clinical trial studies that have tested/are testing drugs in different phases. To the best of our knowledge, the aggregation of the proposed lists of drugs by previous studies has not been extensively exploited towards generating a dynamic reference matrix with enhanced resolution. To fill this knowledge gap, we performed weight-modulated majority voting of the modes of action, initial indications and targeted pathways of the drugs in a well-known repository, namely the Drug Repurposing Hub.

Ranking of cell clusters in a single-cell RNA-sequencing analysis framework using prior knowledge.

Prioritization or ranking of different cell types in a single-cell RNA sequencing (scRNA-seq) framework can be performed in a variety of ways, some of these include: i) obtaining an indication of the proportion of cell types between the different conditions under study, ii) counting the number of differentially expressed genes (DEGs) between cell types and conditions in the experiment or, iii) prioritizing cell types based on prior knowledge about the conditions under study (i.e., a specific disease).

Immediate-Early Genes as Influencers in Genetic Networks and their Role in Alzheimer's Disease.

Immediate-early genes (IEGs) are a class of activity-regulated genes (ARGs) that are transiently and rapidly activated in the absence of de novo protein synthesis in response to neuronal activity. We explored the role of IEGs in genetic networks to pinpoint potential drug targets for Alzheimer's disease (AD). Using a combination of network analysis and genome-wide association study (GWAS) summary statistics we show that (1) IEGs exert greater topological influence across different human and mouse gene networks compared to other ARGs, (2) ARGs are sparsely involved in diseases and significantly more mutational constrained compared to non-ARGs, (3) Many AD-linked variants are in ARGs gene regions, mainly in near FOSB, with an AD risk eQTL that increases expression in cortical areas, (4) holds an influential place in a dense AD multi-omic network and a high AD druggability score.

Oct4 is a gatekeeper of epithelial identity by regulating cytoskeletal organization in skin keratinocytes.

Oct4 is a pioneer transcription factor regulating pluripotency. However, it is not well known whether Oct4 has an impact on epidermal cells. We generated OCT4 knockout clonal cell lines using immortalized human skin keratinocytes to identify a functional role for the protein.

List2Net: Linking multiple lists of biological data in a network context.

Motivation: A common task in scientific research is the comparison of lists or sets of diverse biological entities such as biomolecules, ontologies, sequences and expression profiles. Such comparisons rely, one way or another, on calculating a measure of similarity either by means of vector correlation metrics, set operations such as union and intersection, or specific measures to capture, for example, sequence homology. Subsequently, depending on the data type, the results are often visualized using heatmaps, Venn, Euler, or Alluvial diagrams.

Selective Delivery to Cardiac Muscle Cells Using Cell-Specific Aptamers.

In vivo SELEX is an advanced adaptation of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) that allows the development of aptamers capable of recognizing targets directly within their natural microenvironment. While this methodology ensures a higher translation potential for the selected aptamer, it does not select for aptamers that recognize specific cell types within a tissue. Such aptamers could potentially improve the development of drugs for several diseases, including neuromuscular disorders, by targeting solely the proteins involved in their pathogenesis.

Drug repurposing on Alzheimer's disease through modulation of NRF2 neighborhood.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the most common cause of cognitive decline. The alarming epidemiological features of Alzheimer's disease, combined with the high failure rate of candidate drugs tested in the preclinical phase, impose more intense investigations for new curative treatments. NRF2 (Nuclear factor-erythroid factor 2-related factor 2) plays a critical role in the inflammatory response and in the cellular redox homeostasis and provides cytoprotection in several diseases including those in the neurodegeneration spectrum.

Niclosamide Attenuates Inflammation-Associated Profibrotic Responses in Human Subepithelial Lung Myofibroblasts.

Niclosamide is a commonly used helminthicidic drug for the treatment of human parasitosis by helminths. Recently, efforts have been focusing on repurposing this drug for the treatment of other diseases, such as idiopathic pulmonary fibrosis. Subepithelial lung myofibroblasts (SELMs) isolated from tissue biopsies of patients undergoing surgery for lung cancer were stimulated with TNF-α (50 ng/mL), IL-1α (5 ng/mL), added alone or in combination, and TGF-β (5 ng/mL).

Bacterial Wars-a tool for the prediction of bacterial predominance based on network analysis measures.

Bacterial Wars (BW) is a network-based tool that applies a two-step pipeline to display information on the competition of bacterial species found in the same microbiome. It utilizes antimicrobial peptide (AMP) sequence similarities to obtain a relationship between species. The working hypothesis (putative AMP defense) is that friendly species share sequence similarity among the putative AMPs of their proteomes and are therefore immune to their AMPs.

Preliminary In Vitro and In Vivo Insights of In Silico Candidate Repurposed Drugs for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia. Although a considerably large amount of money has been invested in drug development for AD, no disease modifying treatment has been detected so far. In our previous work, we developed a computational method to highlight stage-specific candidate repurposed drugs against AD.

Methylation status of hypothalamic promoter across puberty.

Makorin RING finger protein 3 (MKRN3) is an important factor located on chromosome 15 in the imprinting region associated with Prader-Willi syndrome. Imprinted is expressed in hypothalamic regions essential for the onset of puberty and mutations in the gene have been found in patients with central precocious puberty. The pubertal process is largely controlled by epigenetic mechanisms that include, among other things, DNA methylation at CpG dinucleotides of puberty-related genes.

PathIN: an integrated tool for the visualization of pathway interaction networks.

PathIN is a web-service that provides an easy and flexible way for rapidly creating pathway-based networks at several functional biological levels: genes, compounds and reactions. The tool is supported by a database repository of reference pathway networks across a large set of species, developed through the freely available information included in the KEGG, Reactome and Wiki Pathways database repositories. PathIN provides networks by means of five diverse methodologies: (a) direct connections between pathways of interest, (b) direct connections as well as the first neighbours of the given pathways, (c) direct connections, the first neighbours and the connections in between them, and (d) two additional methodologies for creating complementary pathway-to-pathway networks that involve additional (missing) pathways that interfere in-between pathways of interest.

A guide to multi-omics data collection and integration for translational medicine.

The emerging high-throughput technologies have led to the shift in the design of translational medicine projects towards collecting multi-omics patient samples and, consequently, their integrated analysis. However, the complexity of integrating these datasets has triggered new questions regarding the appropriateness of the available computational methods. Currently, there is no clear consensus on the best combination of omics to include and the data integration methodologies required for their analysis.

Vir2Drug: a drug repurposing framework based on protein similarities between pathogens.

We draw from the assumption that similarities between pathogens at both pathogen protein and host protein level, may provide the appropriate framework to identify and rank candidate drugs to be used against a specific pathogen. Vir2Drug is a drug repurposing tool that uses network-based approaches to identify and rank candidate drugs for a specific pathogen, combining information obtained from: (a) ranked pathogen-to-pathogen networks based on protein similarities between pathogens, (b) taxonomy distance between pathogens and (c) drugs targeting specific pathogen's and host proteins. The underlying pathogen networks are used to screen drugs by means of specific methodologies that account for either the host or pathogen's protein targets.

Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders.

Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 and the development of ten neurological disorders and three neuropsychiatric disorders by exploring two pathological mechanisms: (i) dysregulation of host biological processes via virus-host protein-protein interactions (PPIs), and (ii) autoreactivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes with host "self" proteins via molecular mimicry. We also identify potential genetic risk factors which in combination with SARS-CoV-2 infection might lead to disease development.

Novel clinical, molecular and bioinformatics insights into the genetic background of autism.

Background: Clinical classification of autistic patients based on current WHO criteria provides a valuable but simplified depiction of the true nature of the disorder. Our goal is to determine the biology of the disorder and the ASD-associated genes that lead to differences in the severity and variability of clinical features, which can enhance the ability to predict clinical outcomes.

Method: Novel Whole Exome Sequencing data from children (n = 33) with ASD were collected along with extended cognitive and linguistic assessments.

The Cyprus Institute of Neurology and Genetics, an emerging paradigm of a gender egalitarian organisation.

Females are underrepresented in the science, technology, engineering, mathematics and medicine (STEMM) disciplines globally and although progress has been made, the gender gap persists. Our aim was to explore gender parity in the context of gender representation and internal collaboration at the Cyprus Institute of Neurology and Genetics (CING), a leading national biomedical organisation accredited as an equal opportunity employer. Towards this aim we (1) explored trends in gender parity within the different departments, positions and qualifications and in student representation in the CING's postgraduate school and, (2) investigated the degree of collaboration between male and female researchers within the Institute and the degree of influence within its co-authorship network.

Immunomodulatory effects of microbiota-derived metabolites at the crossroad of neurodegenerative diseases and viral infection: network-based bioinformatics insights.

Bidirectional cross-talk between commensal microbiota and the immune system is essential for the regulation of immune responses and the formation of immunological memory. Perturbations of microbiome-immune system interactions can lead to dysregulated immune responses against invading pathogens and/or to the loss of self-tolerance, leading to systemic inflammation and genesis of several immune-mediated pathologies, including neurodegeneration. In this paper, we first investigated the contribution of the immunomodulatory effects of microbiota (bacteria and fungi) in shaping immune responses and influencing the formation of immunological memory cells using a network-based bioinformatics approach.

Identifying Novel Osteoarthritis-Associated Genes in Human Cartilage Using a Systematic Meta-Analysis and a Multi-Source Integrated Network.

Osteoarthritis, the most common joint disorder, is characterised by deterioration of the articular cartilage. Many studies have identified potential therapeutic targets, yet no effective treatment has been determined. The aim of this study was to identify and rank osteoarthritis-associated genes and micro-RNAs to prioritise those most integral to the disease.

A Framework for Efficient N-Way Interaction Testing in Case/Control Studies With Categorical Data.

Most common diseases are influenced by multiple gene interactions and interactions with the environment. Performing an exhaustive search to identify such interactions is computationally expensive and needs to address the multiple testing problem. A four-step framework is proposed for the efficient identification of n-Way interactions.

Serum miRNAs as biomarkers for the rare types of muscular dystrophy.

Muscular dystrophies are a group of disorders that cause progressive muscle weakness. There is an increasing interest for the development of biomarkers for these disorders and specifically for Duchene Muscular Dystrophy. Limited research however, has been performed on the biomarkers' development for the most rare muscular dystrophies, like the Facioscapulohumeral Muscular Dystrophy, Limb-Girdle Muscular Dystrophy and Myotonic Dystrophy type 2.